1. Field of the Inventive Concept(s)
The presently disclosed and/or claimed inventive concept(s) relates generally to a hemodynamic monitoring device and methods of making and using same. The hemodynamic monitoring device and its use are particularly well-suited for the measurement of respiratory cycle data simultaneously with at least one of central venous blood pressure and intravascular blood flow velocity and thereafter correlating these measurements to monitor mammalian patients such as humans. In particular, but without limitation, the hemodynamic monitoring device is capable of providing data and information correlating to a fluid responsiveness of the mammalian patient on a continuing basis and in real-time. In one specific but non-limiting embodiment, the respiratory cycle data of the mammalian patient is correlated with at least one of velocity of blood flow in the superior vena cava and central venous blood pressure in order to provide data and information that is thereby calculated and correlated with the fluid responsive state of the patient. In one specific but non-limiting embodiment, the respiratory cycle data of the mammalian patient is correlated with at least one of velocity of blood flow in the superior vena cava in order to provide data and information that is thereby calculated and correlated with the level of right ventricle dysfunction and/or acute pulmonary hypertension in the patient. The hemodynamic device includes sensors to minimally invasively measure the velocity of blood flow in the superior vena cava, central venous blood pressures, and the respiratory cycle data of the patient.
2. Background of the Inventive Concept(s)
Hemodynamic monitoring is a central aspect of cardiovascular diagnosis and titration of care. For example, circulatory shock results primarily in inadequate tissue blood flow. Although most forms of shock may show some increase in cardiac output initially in response to fluid loading, it has been estimated that at least fully one-half of all hemodynamically unstable intensive care unit patients are not preload responsive. See, e.g., Michael, F. et al., “Predicting fluid responsiveness in ICU patients: a critical analysis of the evidence,” Chest 2002; 121:2000-2008, the entire contents of which are hereby incorporated by reference in their entirety. As such, the following fundamental question confronts intensive care providers on a daily basis: will fluid improve perfusion to end organs, or will it cause fluid overload and worsen pulmonary or systemic edema? For example, when treating septic patients volume expansion is often one of the cornerstones of early resuscitation. Volume overload (“hypervolemia”) can have dire consequences such as decreased gas exchange and increased myocardial dysfunction.
A reduction in intravascular volume results in a fall in stroke volume, which is initially compensated for by an increase in heart rate thereby maintaining cardiac output. However, with further volume depletion cardiac output and then blood pressure falls. This is associated with a reduction in organ perfusion. At the organ level, the local autoregulatory mechanism attempts to maintain tissue perfusion.
The patient's hemodynamic state can oftentimes rapidly change as it is influenced by a host of intertwined and interdependent factors. Several studies suggest, for example, that even experienced intensivists using traditional parameters are correct only about half of the time when determining preload responsiveness. As such, static measurements or indices of fluid responsiveness, such as the traditionally used tests of central venous pressure (CVP) and pulmonary artery occlusion pressure (PAOP), often fail as meaningful tools for measuring the patient's hemodynamic state as they do not take into consideration the changes in other systemic interactions that can alter quickly. Indeed, studies in recent years have confirmed that such static measurements have little correlation with fluid responsiveness and are poor clinical indicators.
In many patients, a rapid fluid bolus is a reasonable diagnostic and potentially therapeutic option but, in others (e.g., acute respiratory distress syndrome), it has the potential to cause harm and may delay institution of appropriate therapy. An ideal system would be one in which it is possible to determine if a patient will be fluid-responsive before the fluid is given. The poor predictive value of static measurements and clinical examination has, therefore, led to the investigation of dynamic measurements of fluid responsiveness. In contrast to static measurements, dynamic indices rely mostly on the changing physiology of heart/lung interactions (e.g., measuring cyclic changes in cardiac filling status that are caused by mechanical ventilation) to determine whether a patient is fluid-responsive and will thereby benefit from therapeutic interventions. Indeed, there is growing evidence that dynamic markers (e.g., pulse pressure variation (PPV), systolic pressure variation, aortic blood flow velocity, and superior vena cava collapsibility) more accurately predict fluid responsiveness, than the static measurements traditionally used. Dynamic indices provide for a higher degree of accuracy in fluid responsiveness determinations with significantly reduced invasiveness.
Preload of the heart is defined as the wall stress at the end of diastole, i.e., left ventricular end-diastolic volume (LVEDV). Direct measurement of wall stress in vivo is difficult if not impossible within an emergency medicine department, surgical theater, and/or intensive care environment. Although end diastolic volumes or pressures have been used as proxies of wall stress, both have significant limitations. Perhaps most importantly, an accurate measure of preload at a point in time does not necessarily reflect fluid-responsiveness. An understanding of the Frank-Starling curve (an example of which is shown in FIG. 1) is fundamental to understanding the concept of fluid-responsiveness. The slope of the relationship between ventricular preload and stroke volume (SV) depends on ventricular contractility. As contractility increases, the Frank-Starling curve shifts upward and to the left and increases its slope. Decreasing contractility has the opposite effect. Increasing ventricular preload serves to augment ventricular output predominantly on the steep portion of the curve. As seen in FIG. 1, augmenting ventricular preload on the flat portion of the curve produces minimal increases in stroke volume. In normal physiologic conditions, both ventricles operate on the ascending portion of the Frank-Starling curve. This mechanism provides a functional reserve to the heart in situations of acute stress. In healthy patients, an increase in preload (with volume challenge) results in a significant increase in stroke volume. Furthermore, as a result of altered left ventricular compliance and function, the position of an acutely ill patient on their Frank-Starling curve cannot be predicted from their preload (LVEDV) alone. In critically ill patients it is therefore important not only to determine the patients' preload (LVEDV) but their fluid responsiveness, i.e., to whether the patient will increase their stroke volume or cardiac output with fluid loading. Therefore, even a precise measurement of left ventricular preload does not determine if that left ventricle is fluid-responsive (i.e., if it will increase cardiac output in response to increased volume). Additionally, the relationship between preload and stroke volume is curvilinear rather than linear as can be seen in FIG. 1.
Static Indices of Intravascular Volume
As a static measure of fluid-responsiveness, central venous pressure is frequently used to guide fluid management with reports indicating that over 90% of European intensivists/anesthesiologists used CVP to guide fluid management. The basis for using CVP to guide fluid management comes from the dogma that CVP reflects intravascular volume; specifically, it is widely believed that patients with a low CVP are volume depleted while patients with a high CVP are volume overloaded. A change in CVP following a fluid challenge is thereby used to guide subsequent fluid management decisions. CVP describes the pressure of blood in the thoracic vena cava near the right atrium of the heart. CVP is a good approximation of right atrial pressure, which is a major determinant of right ventricular filling. It has therefore been assumed that CVP is a good indicator of right ventricular preload. Furthermore, as right ventricular stroke volume determines left ventricular filling, the CVP is assumed to be an indirect measure of left ventricular preload. However, because of the changes in venous tone, intrathoracic pressures (positive end expiratory pressure, etc.), left and right ventricular compliance, and geometry that occurs in critically ill patients, it has been found that there is actually a poor relationship between CVP and right ventricular end-diastolic volume. Furthermore, the right ventricular end-diastolic volume may not accurately reflect the patient's position on the Frank-Starling curve and, therefore, their preload reserve.
Historically, medical practice for the measurement of hemodynamic blood flow parameters has been based on the use of a pulmonary artery catheter. This device is highly invasive and requires a catheter to be introduced through a large vein such as the jugular, subclavian, or femoral vein. The catheter is threaded through the right atrium and ventricle of the heart and into the pulmonary artery. The standard pulmonary artery catheter (also known as a “Swan-Ganz” catheter) has two lumens (tubes) and is equipped with an inflatable balloon at the tip, which facilitates its placement into the pulmonary artery through the flow of blood. The balloon, when inflated, causes the catheter to “wedge” in a small pulmonary blood vessel. So wedged, the catheter can provide a measurement of the blood pressure in the left atrium of the heart, termed Left Ventricular End Diastolic Pressure or LVEDP. Modern catheters have multiple lumens (multiple tubes) and have openings along the length to allow administration of inotropes and other drugs directly into the right atrium of the heart. The addition of a small thermistor temperature probe about 3 centimeters behind the tip allows the measurement of blood flow following calibration by means of the injection of a known volume and known temperature of cold fluid. As this cooler fluid passes the thermistor, a brief drop in the blood temperature is recorded. The resulting information can be used to compute and plot a thermodilution curve. If details about the patient's body mass index, core temperature, systolic, diastolic, central venous pressure, and pulmonary artery pressure are known/estimated and thereafter inputted into a diagnostic system connected to the Swan-Ganz catheter, a blood flow and pressure map can be calculated. The procedure is not without risk, and complications can be life threatening. It can lead to arrhythmias, rupture of the pulmonary artery, thrombosis, infection, pneumothorax, bleeding, and other life-threatening complications. Indeed, it was not long after the introduction of the pulmonary artery catheter that studies began to appear demonstrating that PAOP was a poor reflection of preload and more recent studies have demonstrated that pulmonary artery occlusion pressure (PAOP) is a poor predictor of preload and volume responsiveness. PAOP suffers many of the limitations of CVP: (i) PAOP is a measure of left ventricular end-diastolic pressure and not LVEDV or LV preload; (ii) use of PAOP to measure left ventricular preload assumes a direct relationship between the left ventricular end-diastolic pressure and LVEDV while the Frank-Starling principle shows that the pressure-volume curve describing left ventricular compliance is curvilinear; and (iii) alterations in left ventricular compliance shift the pressure-volume curve, for example.
Transesophageal echocardiography has also been used to assess left ventricular dimensions in patients undergoing mechanical ventilation. The left ventricular end-diastolic area (LVEDA) has been shown to correlate with the intrathoracic blood volume (ITBV) and global end-diastolic volume (GEDV), as well as with LVEDV as measured by scintography. For example, an end-diastolic diameter of <25 mm and a LVEDA of <55 cm2 have been used to diagnose hypovolemia. While a number of studies have found the LVEDA to be a good predictor of fluid responsiveness, other studies have failed to replicate such findings. A major limitation of echocardiography is that it provides a snapshot of ventricular function at a single period in time. Recently, a disposable transesophageal echocardiography probe that allows continuous monitoring (a more dynamic measurement) of LV function has been developed (ClariTEE™, ImaCor, Uniondale, N.Y., USA). Such technology allows monitoring of LV volumes and function over time, allowing the clinician to determine the response to various therapeutic interventions.
Dynamic Indices of Intravascular Volume
Dynamic indices, such as pulse pressure variation (PPV) and stroke volume variation (SVV), have traditionally applied a controlled and reversible preload variation and thereafter measured the hemodynamic response. This can be done by observing the cardiovascular response to positive pressure ventilation, or to reversible preload-increasing maneuvers, such as passive leg raising. One such prior art dynamic indices is a measurement of stroke volume variation which examines the differences between the stroke volume during the inspiratory and expiratory phases of ventilation and requires a means to directly or indirectly assess stroke volume. Stroke volume variation processes have traditionally required invasive monitoring such as aortic flow probes. Extravascular assessments of stroke volume have recently become available, however, the PiCCO™ system (Pulsion Medical Systems, Munich, Germany), the LiDCO™ system (LiDCO Group PLC, London, England), and FloTrac™ sensor system (Edwards Lifesciences, Irvine, Calif.) all have monitors that use pulse contour analysis through proprietary formulas that measure cardiac output and stroke volume variation using intravascular arterial pressure waveform analysis.
The principles underlying both PPV and SVV are based on the concept that intermittent positive pressure ventilation induces cyclic changes in the loading conditions of the left (LV) and right (RV) ventricles. Mechanical insufflation decreases preload and increases afterload of the RV. The RV preload reduction is due to the decrease in the venous return pressure gradient that is related in the inspiratory increase in pleural pressure. The increase in RV afterload is related to the inspiratory increase in transpulmonary pressure. The reduction in RV preload and increase in RV afterload both lead to a decrease in RV stroke volume, which is at a minimum at the end of the inspiratory period. The inspiratory reduction in RV ejection leads to a decrease in LV filling after a phase lag of two or three heart beats because of the long blood pulmonary transit time. Thus, the LV preload reduction may induce a decrease in LV stroke volume, which is at its minimum during the expiratory period. The cyclic changes in RV and LV stroke volume are greater when the ventricles operate on the steep rather than the flat portion of the Frank-Starling curve (see FIG. 1). Therefore, the magnitude of the respiratory changes in LV stroke volume is an indicator of biventricular preload dependence. It should be noted that arrhythmias and spontaneous breathing activity may lead to misinterpretations of the respiratory variations in PPV and SVV.
Monitoring of arterial blood pressure measured invasively through an arterial cannula placed in an artery, such as the radial, femoral, dorsalis pedis, or brachial artery, are used with respect to PPV monitoring. The arterial cannula is connected to a sterile, fluid-filled system, which is attached to an electronic pressure transducer. Pressure is constantly monitored beat-by-beat, and a waveform (a graph of pressure against time) can be displayed. Vascular pressure parameters, such as systolic, diastolic, and mean arterial pressure, are derived and displayed simultaneously for pulsatile waveforms. Such devices utilize pulse contour or pulse pressure wave analysis where the area under the systolic pressure wave curve is integrated, or wave characteristics are analyzed, and, when calibrated against either dye dilution or thermodilution, provide estimates of blood flow volume.
Cannulation for invasive vascular pressure monitoring is, however, associated with complications such as extravasation, thrombosis, and infection among other life threatening conditions. Patients with invasive arterial monitoring require very close supervision, as there is a danger of severe bleeding if the arterial line becomes disconnected. Peripheral vascular pressure monitoring devices are also known to be problematic in monitoring rapid changes in patients who are hemodynamically unstable. As such, these devices may and do lead to erroneous cardiac output measurements during the administration of vasoactive drugs, during loss of circulating volume, e.g., hemorrhage, insufflation of the abdomen for laparoscopic surgery, pathophysiological diseases resulting in abnormal arterial pressure waves, and positional changes during surgery. As but one example, drugs which create vasoconstriction result in an increase in systemic resistance and thus an increase in pressure which is interpreted as an increase in flow, whereas blood flow typically decreases as systemic resistance increases as the heart is acting to pump against increased resistance. Conversely, drugs which have a vasodilation effect result in a decrease in resistance to blood flow and typically blood pressure falls which is interpreted as a reduction in flow, whereas blood flow typically increases as systemic resistance decreases as the heart is acting to pump against a reduced resistance. Calibration is essential for absolute value accuracy and, in operating room conditions such calibration is complex to perform, is time consuming, needs to be repeated frequently, introduces chemical agents which may be toxic, and may be of limited accuracy in the presence of other drugs administered during patient treatment. As with extravascular ultrasound technologies (discussed further below), arterial blood pressure monitoring also requires the presence of a trained and experienced operator.
It has been found that superior vena cava (SVC) diameter is affected by the large fluctuations in intrathoracic pressure caused by positive pressure variation. A recent study by Vieillard-Baron et al., for example, noted a clustering of baseline SVC collapsibility between responders (with SVC collapse of 60% or more) and nonresponders (in whom SVC varied by 30% or less). “Superior vena cava collapsibility as a gauge of volume status in ventilated septic patients,” Intensive Care Med 2004; 30:1734-39, the entire contents of which are hereby incorporated by reference in their entirety. This finding results in a specificity of 100% and a sensitivity of 90% for predicting a significant increase in cardiac output when the SVC collapsibility exceeds 36%. A disadvantage in monitoring SVC diameter variation as a dynamic indices of fluid responsiveness is that it requires transesophageal echocardiography which has all of the same disadvantages and limitations of other types of extravascular ultrasound—sensitivity to movement, user training and maintenance, and oftentimes difficult to visualize anatomical structures.
Extravascular Doppler measurements of variations of stroke volume have been used as an ultrasound technique for assessing dynamic indices of volume responsiveness. Fluctuations in stroke volume associated with ventilator cycling are greater in the hypovolemic patient than in the completely resuscitated patient. See, e.g., Feissel M. et al., “Respiratory changes in aortic blood velocity as an indicator of fluid responsiveness in ventilated patients with septic shock,” Chest 2001; 119:867-73, the entire contents of which are hereby incorporated by reference in their entirety. The extravascular measurement of stroke volume by use of ultrasound and the Doppler principle relies upon the use of a probe containing piezoelectric crystals that are caused to emit either continuous wave or pulse wave ultrasound extravascularly into an adjacent arterial blood vessel. The probe may be located either in the esophagus, trachea, or is placed on the body surface in a position where an artery can be monitored. The velocity of the blood flow is calculated using the Doppler equation:v=(c)(fD)/2(fT)Cos Θwhere v is the velocity of the red blood cells, c is the speed of the ultrasound waves through body tissues, fD is the Doppler frequency shift, fT is the transmitted frequency of the ultrasound and Cos Θ is the cosine of the angle of insonation between the sound beam axis and the direction of blood flow. Such extravascular flow based measurements are, however, difficult to perform and require the presence of an operator that is capable of maintaining properly placement, alignment, and calibration of the ultrasound probe. The ultrasound beam is directional and is sensitive to movement, which requires the operator to check the beam's focus and thus the device cannot be considered to be providing continuous monitoring without operator attendance.Acute Pulmonary Hypertension
Many complex medical disorders managed in intensive care units (ICU) are associated with an elevation of pulmonary arterial pressure (PAP). In some circumstances, serious and prolonged elevation of PAP progresses to severe acute pulmonary hypertension, leading to life threatening complications including, but not limited to, refractory systemic arterial hypotension, severe hypoxemia, right ventricular (RV) dysfunction and failure, and ultimately resulting in cardiogenic and/or obstructive shock and death. Clinical presentation, physical exam, electrocardiogram, ultrasound, and chest radiography can suggest pulmonary circulation abnormality. However, those data are not either specific enough or continuous to be useful in early diagnoses of acute pulmonary hypertension in intensive care units, nor for determining whether signs of acute pulmonary hypertension are hemodynamically significant. The use of Pulmonary Artery Catheter (PAC) capable of PAP monitoring has been significantly reduced due to its invasiveness and related safety concerns. Pulmonary hypertension is usually recognized when the patient develops obvious signs of progressive right ventricular failure, and during hemodynamic monitoring by echocardiogram or a pulmonary artery catheterization. Unfortunately, in most cases acute pulmonary hypertension remains under diagnosed or undiagnosed and treatment begins only after serious complications have developed. See, for example, Tsapenko et al., “Arterial pulmonary hypertension in noncardiac intensive care unit,” Vascular Health and Risk Management 2008:4(5) 1043-1060, the entire contents of which are hereby incorporated by reference in their entirety.
Clinically significant onset of acute pulmonary hypertension causes the right ventricle of the heart to start to dilate. Higher pressure in the pulmonary artery (behind the right heart) may overload the right ventricle, causing the right ventricle to dilate or even fail. Even subtle dilation of the right ventricle may cause tricuspid valve insufficiency, that is, dysfunction of the valve between the right ventricle and the right atrium. The insufficiency of the tricuspid valve may cause backward leakage during right ventricle systole (that is, contraction). The backward leakage is known as Tricuspid Regurgitation (TR). The stronger the leak means the stronger the dilation of the right ventricle and the higher the level of right heart dysfunction caused by acute pulmonary hypertension onset. Current systems may monitor TR at the tricuspid valve using non-invasive TTE or TEE probes, producing data interpreted by sono specialists.
Given the limitations and complications of using current hemodynamic monitoring devices and methodologies, there is a need in the art for an improved method and apparatus for minimally invasive monitoring of the fluid-responsiveness of a patient continuously and in real time using dynamic indices. The presently disclosed and/or claimed inventive concept(s) disclose a method and apparatus that combines measurement of intravascular blood flow velocities simultaneously with respiratory cycle data to provide monitoring of a patient's fluid-responsive state and/or level of right ventricle dysfunction and/or acute pulmonary hypertension in a minimally invasive and operator independent process, thereby overcoming one or more of the aforementioned drawbacks found in the prior art apparatuses and techniques.